US11961590B2ActiveUtilityPatentIndex 45
Methods for preparing optimal combination of oligonucleotides
Est. expiryApr 17, 2037(~10.8 yrs left)· nominal 20-yr term from priority
Inventors:JANG MI HYUN
G16B 25/20C12N 15/1089G06F 17/12G16B 30/00C12Q 1/6806C12Q 1/6876G16B 40/00
45
PatentIndex Score
0
Cited by
27
References
11
Claims
Abstract
The present invention relates to optimization logic for preparing an optimal combination of oligonucleotides hybridized with a plurality of target nucleic acid sequences, in a completely different approach from conventional methods, i.e., empirical and manual methods. In addition, the optimization logic of the present invention may be used to (i) preparing an oligonucleotide combination used to detect a plurality of target nucleic acid sequences with a target coverage of interest, (ii) selecting target nucleic acid sequences to be detected by a multiplex target detection with a highest target coverage by using a limited number of oligonucleotides, and (iii) determining a conserved region in a plurality of target nucleic acid sequences.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A computer-implemented method for preparing a combination of oligonucleotides used to detect a plurality of target nucleic acid sequences with a target coverage of interest from a pool of oligonucleotides, comprising:
(a) preparing the plurality of target nucleic acid sequences;
(b) preparing the pool of oligonucleotides to be hybridized with the plurality of target nucleic acid sequences;
(c) selecting from the pool of oligonucleotides a combination of a minimum number of oligonucleotides with the target coverage of interest for the plurality of target nucleic acid sequences; wherein the selection of the combination of the minimum number of oligonucleotides is performed to achieve the following objective formula 1 together with satisfying the following constraint formulas 1 and 2, or the constraint formula 2; and,
(d) preparing the combination of the minimum number of oligonucleotides selected in step (c); and
Min
:
∑
p
=
1
a
x
p
Objective
formula
1
wherein Min: represents minimization, x p is a binary variable consisting of a non-selection value (X non-sel ) and a selection value (x sel ) for whether or not an oligonucleotide p is selected, and p is a serial number of the oligonucleotide p ranging from 1 to a;
∑
s
=
1
b
c
s
≥
m
×
S
Constraint
formula
1
wherein c s is a binary variable consisting of a non-coverage value (c non-cov ) and a coverage value (c cov ) for whether or not a target nucleic acid sequence s is covered, m is a target coverage of interest with a value of 0<m<1, S is the total number of the plurality of target nucleic acid sequences, and s is a serial number of a target nucleic acid sequence s ranging from 1 to b;
∑
p
=
1
a
y
s
,
p
x
p
≥
c
s
for
all
s
Constraint
formula
2
wherein y s,p is a binary constant consisting of a non-coverage value (y non-cov ) and a coverage value (y cov ) representing whether or not a target nucleic acid sequence s is covered by an oligonucleotide p; x p is a binary variable for whether or not an oligonucleotide p is selected; c s is a binary variable for whether or not a target nucleic acid sequence s is covered in which c s is a coverage value (c cov ) when the target coverage of interest is 100% and c s is a non-coverage value (c non-cov ) and a coverage value (c cov ) when the target coverage of interest is less than 100%; and for all s represents application to all of target nucleic acid sequences s.
2. The method according to claim 1 , wherein the method is performed to achieve the objective formula 1 together with satisfying the constraint formulas 1 and 2 when the target coverage of interest is less than 100%, whereby the combination of the minimum number of oligonucleotides is selected and target nucleic acid sequences covered by the selected combination of the minimum number of oligonucleotides are selected among the plurality of target nucleic acid sequences.
3. The method according to claim 1 , wherein the method is performed to achieve the objective formula 1 together with satisfying the constraint formula 2 when the target coverage of interest is 100%.
4. The method according to claim 1 , wherein the binary variable c s of the constraint formula 2 is x a+s in which a is the last serial number of an oligonucleotide p and s is a serial number of a target nucleic acid sequence s ranging from 1 to b.
5. The method according to claim 1 , wherein the non-selection value (x non-sel ) and the selection value (x sel ) of the x p are 0 and 1, respectively.
6. The method according to claim 1 , wherein the non-coverage value (c non-cov ) and the coverage value (c cov ) of the c s are 0 and 1, respectively.
7. The method according to claim 1 , wherein the non-coverage value (y non-cov ) and the coverage value (y cov ) of the y s,p are 0 and 1, respectively.
8. The method according to claim 1 , wherein the plurality of target nucleic acid sequences are a plurality of nucleic acid sequences having sequence similarity for one target nucleic acid molecule exhibiting genetic diversity.
9. The method according to claim 1 , wherein the plurality of target nucleic acid sequences are a plurality of nucleic acid sequences from a plurality of organisms corresponding to homologues having the same function, the same structure, or the same gene name.
10. The method according to claim 1 , wherein the pool of oligonucleotides comprises oligonucleotides that are hybridized with at least one sequence of the plurality of target nucleic acid sequences, and the oligonucleotides in the pool of oligonucleotides differ in a hybridization region and/or length from each other.
11. A non-transitory computer readable storage medium containing instructions to configure a processor to perform a method for preparing a combination of oligonucleotides used to detect a plurality of target nucleic acid sequences with a target coverage of interest from a pool of oligonucleotides, the method comprising:
selecting from the pool of oligonucleotides a combination of the minimum number of oligonucleotides with the target coverage of interest for the plurality of target nucleic acid sequences; wherein the selection of the combination of the minimum number of oligonucleotides is performed to achieve the following objective formula 1 together with satisfying the following constraint formulas 1 and 2, or the constraint formula 2:
Min
:
∑
p
=
1
a
x
p
Objective
formula
1
wherein Min: represents minimization, x p is a binary variable consisting of a non-selection value (x non-sel ) and a selection value (x sel ) for whether or not an oligonucleotide p is selected, and p is a serial number of the oligonucleotide p ranging from 1 to a;
∑
s
=
1
b
c
s
≥
m
×
S
Constraint
formula
1
wherein c s is a binary variable consisting of a non-coverage value (c non-cov ) and a coverage value (c cov ) for whether or not a target nucleic acid sequence s is covered, m is a target coverage of interest with a value of 0<m<1, S is the total number of the plurality of target nucleic acid sequences, and s is a serial number of a target nucleic acid sequence s ranging from 1 to b;
∑
p
=
1
a
y
s
,
p
x
p
≥
c
s
for
all
s
Constraint
formula
2
wherein y s,p is a binary constant consisting of a non-coverage value (y non-cov ) and a coverage value (y cov ) representing whether or not a target nucleic acid sequence s is covered by an oligonucleotide p; x p is a binary variable for whether or not an oligonucleotide p is selected; c s is a binary variable for whether or not a target nucleic acid sequence s is covered in which c s is a coverage value (c cov ) when the target coverage of interest is 100% and c s is a non-coverage value (c non-cov ) and a coverage value (c cov ) when the target coverage of interest is less than 100%; and for all s represents application to all of target nucleic acid sequences s.Cited by (0)
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